MPI for Heart and Lung Research
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Project leaders: Dr. Julián Albárran Juárez, Dr. Shuya Liu, Dr. Lei Wang, Dr. Akiko Nakayama, Dr. Ramesh Chennupati, Dr. Sheng-Peng Wang, Dr. Kerstin Troidl

PhD Students: András Iring, Rui Li, Alan LeMercier

Technical Assistants: Ulrike Schlapp, Claudia Ullmann, Christina Winterbauer

Vascular signaling

Mechanisms underlying fluid shear stress-induced NO-formation (Wang et al., 2015). Fluid shear stress results in the opening of the mechanosensitive cation channel Piezo1. This leads to the release of ATP from endothelial cells (in part mediated by pannexins). ATP then acts through the P2Y2 receptor to activate via Gq/G11-mediated signaling the mechanotransduction complex consisting of PECAM-1, VE-cadherin and VEGFR2. For details see Wang et al., 2015 and Wang et al., 2016.

Work in this research area focused on the role of G-protein mediated signaling processes in the regulation of vascular permeability, vascular tone and vessel remodeling. It turned out that the Gq/G11-mediated signal transduction pathway does not only play an important role in the endothelial barrier (Korhonen et al, 2009) but also in the transmission of shear forces resulting from vascular flow. The latter process involves the endothelial ATP-receptor P2Y2 (Wang et al., 2015). Progress was also made in the analysis of the complex regulation of vascular smooth muscle (VSM) function through different G-protein mediated signaling pathways. While Ca2+-mediated signaling and Ca2+-independent, Rho-dependent signaling synergize in the positive regulation of vascular tone especially under pathological conditions (Wirth et al, 2008) both pathways play antagonistic roles in the regulation of VSM cell differentiation during vascular remodeling (Althoff et al, 2012). 

Literature

Wang, SP, Chennupati R, Iring A, Kaur H, Wettschureck N, Offermanns S. (2016) Endothelial Piezo1 controls blood pressure by mediating flow-induced ATP release. J. Clin. Invest. [epub ahead of print]

Wang S, Iring A, Strilic B, Albarrán Juárez J, Kaur H, Troidl K, Tonack S, Burbiel JC, Müller CE, Fleming I, Lundberg JO, Wettschureck N, Offermanns S (2015). P2Y2 and Gq/G11 control blood pressure by mediating endothelial mechanotransduction. J. Clin. Invest. 125: 3077-3086.

Althoff TF, Albarrán Juárez J, Troidl K, Tang C, Wang S, Wirth A, Takefuji M, Wettschureck N, Offermanns S (2012). Procontractile G-protein-mediated signaling pathways antagonistically regulate smooth muscle differentiation in vascular remodeling. J. Exp. Med. 209, 2277-90

Korhonen H, Fisslthaler B, Moers A, Wirth A, Habermehl D, Wieland T, Schütz G, Wettschureck N, Fleming I, Offermanns S (2009). Anaphylactic shock depends on endothelial Gq/G11. J Exp Med, 206, 411-420

Wirth A, Benyó Z, Lukasova M, Leutgeb B, Wettschureck N, Gorbey S, Őrsy P, Horváth B, Maser-Gluth C, Greiner E, Lemmer B, Schütz G, Gutkind S, Offermanns S (2008). G12/G13-LARG-mediated signalling in vascular smooth muscle is required for salt-induced hypertension. Nat Med 14, 64-68